Post-Transplant Glycaemic Changes in the Renal Allograft Recipient with Prolonged Release Tacrolimus compared to the Immediate Release: A Randomised Controlled Clinical Trial

To understand the changes in the glucose and lipid metabolism, graft function(eGFR), markers of beta cell damage and insulin resistance in a kidney transplant recipient with Prolonged Release tacrolimus compared to the Immediate Release tacrolimus. We hypothesize that the incidence of PTDM will be reduced by at least 50% (30% to 15%) in a non-genotype stratified population by using a Tac-PR formulation compared to the Tac-IR formulation. Further, we believe that the effect will be more pronounced in recipients with pre-existing risk for PTDM in the pre-transplant period, and our study may be able to elucidate the biomarkers for early detection of PTDM. Study will be conducted in the Renal Transplant Ward and ICU, Nehru hospital, PGIMER, Chandigarh. The potential patients/legal attendant will be approached and asked for their voluntariness to participate in the study. The study details will then be described in their vernacular language and patient information sheet will be filled.  A written informed consent will be taken from all the participants. The patients will be screened for eligibility as per inclusion/exclusion criteria.

 The pretransplant biomarker evaluations will include OGTT test (for glucose, insulin, C-peptide, and proinsulin) and fasting lipid profile; these will be repeated 45 days after the surgery. The patients will be randomized to receive Tac-IR or Tac-PR formulations in 1:1 ratio. The starting dose of the drug for the Tac-IR will be 0.1- 0.2mg/kg/day, 24 to 48 hours prior to transplantation. The same dose of the drug will be started for the Tac-PR group with the required titration for the target C0 concentration window of 10-15ng/ml for the first 30 days and 8-10ng/ml thereafter. Dose titration will be performed every three days until the target window is reached. The patients will be advised to perform the C0 twice a week in the first 4 week and weekly thereafter.

The recruited participants in the primary study would be invited to participate in the pharmacokinetic study which involves multiple blood sample collection over a 12-hour/24-hour period. They will be housed in the Clinical Pharmacology Unit of the Department of Pharmacology. 2ml blood samples will be obtained in EDTA vial before the routine drug administration for the patient. The drug will be administered in a supervised manner, and 2 ml of blood sample will be obtained in EDTA vials over a single dosing interval at 0.5, 1.5, 2, 4,8,12 and 24 hours. All the samples will be stored at 4C, and the quantification for whole blood tacrolimus will be performed within seven days of collection by LCMS/MS method (AB Sciex 3500) in the Department of Pharmacology.